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3PC-022 Formulation and quality control of a bisoprolol 0.5 mg/ml oral solution for paediatric use
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  1. H Linxweiler,
  2. J Boventer,
  3. A Walter,
  4. I Krämer
  1. University Medical Center Johannes Gutenberg University Mainz, Pharmacy Department, Mainz, Germany

Abstract

Background and Importance Bisoprolol is a beta blocker indicated for the treatment of heart failure in paediatric patients. There are no licensed bisoprolol containing paediatric dosage forms available in the EU. Pharmacy preparation of patient individually dosed bisoprolol capsules is common practice by using licensed bisoprolol tablets as starting material. However, the preparation and use of bisoprolol oral liquids are the gold standard for paediatric patients because they allow body weight oriented dosing for different age groups. So far, there is no published information regarding the formulation, quality control, and stability of pharmacy-prepared bisoprolol oral solutions.

Aim and Objectives The aim of this project was to formulate a bisoprolol fumarate 0.5 mg/mL oral solution for paediatric use, establish suitable quality-control measures, and to perform stability tests.

Material and Methods Bisoprolol oral solution was formulated in analogy to propranolol hydrochloride oral solution described in Neues Rezeptur-Formularium 2015/1, Germany. Efficacy of antimicrobial preservation was tested regarding to Ph. Eur. 5.3.1 by an external lab. A stability indicating RP-HPLC method was established and validated based on the known method of Joshi et al.1

Results 100 mL bisoprolol fumarate 0.5 mg/mL oral solution contain bisoprolol fumarate 0.05 g as active ingredient as well as potassium sorbate 0.15 g, anhydrous citric acid 0.07 g, sucrose 25 g, raspberry flavour 0.1 g, and purified water 84.33 g as excipients. Antimicrobial preservation regarding Ph. Eur. 5.3.1 was demonstrated. After a 6 months period the bisoprolol concentration amounted to 103% ± 1% of the initial concentration and the pH remained unchanged (4.6).

Conclusion and Relevance Sweetened and flavoured bisoprolol fumarate oral solution was successfully developed as pharmacy preparation suitable for preparation in stock. Adequate in-use preservation is given and stability is proven for at least 6 months. A second version of bisoprolol oral solution without sucrose and raspberry flavour is under development.

Reference

  1. Joshi SJ et al. RP-HPLC method for simultaneous estimation of bisoprolol fumarate and hydrochlorothiazide in tablet formulation. J Pharm Biomed Anal. 2010 Jul 8;52(3):362–71.

Conflict of Interest No conflict of interest.

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